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dc.contributor.authorCox, Daviden
dc.contributor.authorGottschalk, Michael Gerden
dc.contributor.authorStelzhammer, Viktoriaen
dc.contributor.authorWesseling, Hendriken
dc.contributor.authorCooper, Jasonen
dc.contributor.authorBahn, Sabineen
dc.date.accessioned2017-02-15T14:23:17Z
dc.date.available2017-02-15T14:23:17Z
dc.date.issued2016-11en
dc.identifier.issn1562-2975
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/262537
dc.description.abstract$\textbf{Objectives:}$ Rodent models of major depressive disorder (MDD) are indispensable when screening for novel treatments, but assessing their translational relevance with human brain pathology has proved difficult. $\textbf{Methods:}$ Using a novel systems approach, proteomics data obtained from post-mortem MDD anterior prefrontal cortex tissue ($n$ = 12) and matched controls ($n$ = 23) were compared with equivalent data from three commonly used preclinical models exposed to environmental stressors (chronic mild stress, prenatal stress and social defeat). Functional pathophysiological features associated with depression-like behaviour were identified in these models through enrichment of protein-protein interaction networks. A cross-species comparison evaluated which model(s) represent human MDD pathology most closely. $\textbf{Results:}$ Seven functional domains associated with MDD and represented across at least two models such as "carbohydrate metabolism and cellular respiration" were identified. Through statistical evaluation using kernel-based machine learning techniques, the social defeat model was found to represent MDD brain changes most closely for four of the seven domains. $\textbf{Conclusions:}$ This is the first study to apply a method for directly evaluating the relevance of the molecular pathology of multiple animal models to human MDD on the functional level. The methodology and findings outlined here could help to overcome translational obstacles of preclinical psychiatric research.
dc.description.sponsorshipStanley Medical Research Institute (Grant ID: 424 07R-1888), NEWMEDS Innovative Medicines Initiative (Grant ID: FP7/2007-13)
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.language.isoenen
dc.publisherTaylor & Francis
dc.titleEvaluation of molecular brain changes associated with environmental stress in rodent models compared to human major depressive disorder: A proteomic systems approach.en
dc.typeArticle
prism.endingPage12
prism.publicationDate2016en
prism.publicationNameThe world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatryen
prism.startingPage1
dc.identifier.doi10.17863/CAM.7805
dcterms.dateAccepted2016-10-18en
rioxxterms.versionofrecord10.1080/15622975.2016.1252465en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2016-11en
dc.identifier.eissn1814-1412
rioxxterms.typeJournal Article/Reviewen
rioxxterms.freetoread.startdate2017-10-27


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